首页 > 最新文献

Acta Neuropathologica最新文献

英文 中文
Key features of choroidal abnormalities in neurofibromatosis type 1, a commentary on “Histologic correlates of “choroidal abnormalities” in neurofibromatosis type 1 (NF1)” 1 型神经纤维瘤病脉络膜异常的主要特征,对《1 型神经纤维瘤病 (NF1) 中 "脉络膜异常 "的组织学相关性》的评论。
IF 9.3 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-16 DOI: 10.1007/s00401-024-02783-1
Luca Lucchino, Fabiana Mallone, Magda Gharbiya, Ludovico Alisi
{"title":"Key features of choroidal abnormalities in neurofibromatosis type 1, a commentary on “Histologic correlates of “choroidal abnormalities” in neurofibromatosis type 1 (NF1)”","authors":"Luca Lucchino, Fabiana Mallone, Magda Gharbiya, Ludovico Alisi","doi":"10.1007/s00401-024-02783-1","DOIUrl":"10.1007/s00401-024-02783-1","url":null,"abstract":"","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":null,"pages":null},"PeriodicalIF":9.3,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-024-02783-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cryo-EM structures of cotton wool plaques’ amyloid β and of tau filaments in dominantly inherited Alzheimer disease 显性遗传阿尔茨海默病中棉絮斑块淀粉样β和tau丝的冷冻电子显微镜结构。
IF 9.3 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-15 DOI: 10.1007/s00401-024-02786-y
Md Rejaul Hoq, Anllely Fernandez, Frank S. Vago, Grace I. Hallinan, Sakshibeedu R. Bharath, Daoyi Li, Kadir A. Ozcan, Holly J. Garringer, Wen Jiang, Ruben Vidal, Bernardino Ghetti

Cotton wool plaques (CWPs) have been described as features of the neuropathologic phenotype of dominantly inherited Alzheimer disease (DIAD) caused by some missense and deletion mutations in the presenilin 1 (PSEN1) gene. CWPs are round, eosinophilic amyloid-β (Aβ) plaques that lack an amyloid core and are recognizable, but not fluorescent, in Thioflavin S (ThS) preparations. Amino-terminally truncated and post-translationally modified Aβ peptide species are the main component of CWPs. Tau immunopositive neurites may be present in CWPs. In addition, neurofibrillary tangles coexist with CWPs. Herein, we report the structure of Aβ and tau filaments isolated from brain tissue of individuals affected by DIAD caused by the PSEN1 V261I and A431E mutations, with the CWP neuropathologic phenotype. CWPs are predominantly composed of type I Aβ filaments present in two novel arrangements, type Ic and type Id; additionally, CWPs contain type I and type Ib Aβ filaments. Tau filaments have the AD fold, which has been previously reported in sporadic AD and DIAD. The formation of type Ic and type Id Aβ filaments may be the basis for the phenotype of CWPs. Our data are relevant for the development of PET imaging methodologies to best detect CWPs in DIAD.

棉絮斑(CWPs)被描述为显性遗传性阿尔茨海默病(DIAD)神经病理学表型的特征,该病是由 Presenilin 1(PSEN1)基因的某些错义和缺失突变引起的。CWPs是缺乏淀粉样核心的圆形嗜酸性淀粉样-β(Aβ)斑块,在硫黄素S(ThS)制剂中可被识别,但无荧光。氨基酸末端截短和翻译后修饰的 Aβ 肽是 CWPs 的主要成分。CWPs 中可能存在 Tau 免疫阳性神经元。此外,神经纤维缠结也与 CWPs 共存。在此,我们报告了从因 PSEN1 V261I 和 A431E 突变导致的 DIAD 患者脑组织中分离出的 Aβ 和 tau 纤维的结构,这些患者具有 CWP 神经病理学表型。CWPs主要由I型Aβ丝组成,并以Ic型和Id型两种新的排列方式存在;此外,CWPs还含有I型和Ib型Aβ丝。Tau丝具有AD折叠,这在散发性AD和DIAD中已有报道。Ic 型和 Id 型 Aβ 细丝的形成可能是 CWPs 表型的基础。我们的数据与 PET 成像方法的发展相关,以最好地检测 DIAD 中的 CWPs。
{"title":"Cryo-EM structures of cotton wool plaques’ amyloid β and of tau filaments in dominantly inherited Alzheimer disease","authors":"Md Rejaul Hoq,&nbsp;Anllely Fernandez,&nbsp;Frank S. Vago,&nbsp;Grace I. Hallinan,&nbsp;Sakshibeedu R. Bharath,&nbsp;Daoyi Li,&nbsp;Kadir A. Ozcan,&nbsp;Holly J. Garringer,&nbsp;Wen Jiang,&nbsp;Ruben Vidal,&nbsp;Bernardino Ghetti","doi":"10.1007/s00401-024-02786-y","DOIUrl":"10.1007/s00401-024-02786-y","url":null,"abstract":"<div><p>Cotton wool plaques (CWPs) have been described as features of the neuropathologic phenotype of dominantly inherited Alzheimer disease (DIAD) caused by some missense and deletion mutations in the presenilin 1 (<i>PSEN1</i>) gene. CWPs are round, eosinophilic amyloid-β (Aβ) plaques that lack an amyloid core and are recognizable, but not fluorescent, in Thioflavin S (ThS) preparations. Amino-terminally truncated and post-translationally modified Aβ peptide species are the main component of CWPs. Tau immunopositive neurites may be present in CWPs. In addition, neurofibrillary tangles coexist with CWPs. Herein, we report the structure of Aβ and tau filaments isolated from brain tissue of individuals affected by DIAD caused by the <i>PSEN1 V261I</i> and <i>A431E</i> mutations, with the CWP neuropathologic phenotype. CWPs are predominantly composed of type I Aβ filaments present in two novel arrangements, type Ic and type Id; additionally, CWPs contain type I and type Ib Aβ filaments. Tau filaments have the AD fold, which has been previously reported in sporadic AD and DIAD. The formation of type Ic and type Id Aβ filaments may be the basis for the phenotype of CWPs. Our data are relevant for the development of PET imaging methodologies to best detect CWPs in DIAD.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":null,"pages":null},"PeriodicalIF":9.3,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11327195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Current insights and assumptions on α-synuclein in Lewy body disease 目前对路易体疾病中α-突触核蛋白的认识和假设。
IF 9.3 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-14 DOI: 10.1007/s00401-024-02781-3
Rehana K. Leak, Rachel N. Clark, Muslim Abbas, Fei Xu, Jeffrey L. Brodsky, Jun Chen, Xiaoming Hu, Kelvin C. Luk

Lewy body disorders are heterogeneous neurological conditions defined by intracellular inclusions composed of misshapen α-synuclein protein aggregates. Although α-synuclein aggregates are only one component of inclusions and not strictly coupled to neurodegeneration, evidence suggests they seed the propagation of Lewy pathology within and across cells. Genetic mutations, genomic multiplications, and sequence polymorphisms of the gene encoding α-synuclein are also causally linked to Lewy body disease. In nonfamilial cases of Lewy body disease, the disease trigger remains unidentified but may range from industrial/agricultural toxicants and natural sources of poisons to microbial pathogens. Perhaps due to these peripheral exposures, Lewy inclusions appear at early disease stages in brain regions connected with cranial nerves I and X, which interface with inhaled and ingested environmental elements in the nasal or gastrointestinal cavities. Irrespective of its identity, a stealthy disease trigger most likely shifts soluble α-synuclein (directly or indirectly) into insoluble, cross-β-sheet aggregates. Indeed, β-sheet-rich self-replicating α-synuclein multimers reside in patient plasma, cerebrospinal fluid, and other tissues, and can be subjected to α-synuclein seed amplification assays. Thus, clinicians should be able to capitalize on α-synuclein seed amplification assays to stratify patients into potential responders versus non-responders in future clinical trials of α-synuclein targeted therapies. Here, we briefly review the current understanding of α-synuclein in Lewy body disease and speculate on pathophysiological processes underlying the potential transmission of α-synucleinopathy across the neuraxis.

路易体疾病是一种由畸形的α-突触核蛋白聚集体构成的细胞内包涵体所定义的神经系统疾病。虽然α-突触核蛋白聚集体只是内含物的一个组成部分,与神经变性并无严格关联,但有证据表明,它们是路易体病理学在细胞内和细胞间传播的种子。α-突触核蛋白编码基因的基因突变、基因组增殖和序列多态性也与路易体疾病有因果关系。在路易体病的非家族病例中,疾病的诱因仍未确定,但可能包括工业/农业毒物、天然毒物来源和微生物病原体。也许是由于这些外周接触,路易包涵体在疾病早期出现在与颅神经 I 和 X 相连的脑区,这些脑区与鼻腔或胃肠道中吸入和摄入的环境因素相接。无论其身份如何,隐性疾病诱因最有可能(直接或间接)将可溶的α-突触核蛋白转变为不溶的、交叉β片状聚集体。事实上,患者血浆、脑脊液和其他组织中都存在富含β片的自我复制α-突触核蛋白多聚体,并可进行α-突触核蛋白种子扩增试验。因此,在未来的α-突触核蛋白靶向疗法临床试验中,临床医生应能利用α-突触核蛋白种子扩增检测将患者分为潜在应答者和非应答者。在此,我们简要回顾了目前对路易体病中α-突触核蛋白的认识,并推测了α-突触核蛋白病可能在神经轴中传播的病理生理过程。
{"title":"Current insights and assumptions on α-synuclein in Lewy body disease","authors":"Rehana K. Leak,&nbsp;Rachel N. Clark,&nbsp;Muslim Abbas,&nbsp;Fei Xu,&nbsp;Jeffrey L. Brodsky,&nbsp;Jun Chen,&nbsp;Xiaoming Hu,&nbsp;Kelvin C. Luk","doi":"10.1007/s00401-024-02781-3","DOIUrl":"10.1007/s00401-024-02781-3","url":null,"abstract":"<div><p>Lewy body disorders are heterogeneous neurological conditions defined by intracellular inclusions composed of misshapen α-synuclein protein aggregates. Although α-synuclein aggregates are only one component of inclusions and not strictly coupled to neurodegeneration, evidence suggests they seed the propagation of Lewy pathology within and across cells. Genetic mutations, genomic multiplications, and sequence polymorphisms of the gene encoding α-synuclein are also causally linked to Lewy body disease. In nonfamilial cases of Lewy body disease, the disease trigger remains unidentified but may range from industrial/agricultural toxicants and natural sources of poisons to microbial pathogens. Perhaps due to these peripheral exposures, Lewy inclusions appear at early disease stages in brain regions connected with cranial nerves I and X, which interface with inhaled and ingested environmental elements in the nasal or gastrointestinal cavities. Irrespective of its identity, a stealthy disease trigger most likely shifts soluble α-synuclein (directly or indirectly) into insoluble, cross-β-sheet aggregates. Indeed, β-sheet-rich self-replicating α-synuclein multimers reside in patient plasma, cerebrospinal fluid, and other tissues, and can be subjected to α-synuclein seed amplification assays. Thus, clinicians should be able to capitalize on α-synuclein seed amplification assays to stratify patients into potential responders <i>versus</i> non-responders in future clinical trials of α-synuclein targeted therapies. Here, we briefly review the current understanding of α-synuclein in Lewy body disease and speculate on pathophysiological processes underlying the potential transmission of α-synucleinopathy across the neuraxis.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":null,"pages":null},"PeriodicalIF":9.3,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11324801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141974781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
ASXL1 inactivation and reduced H3K27me3 across central nervous system tumors 中枢神经系统肿瘤中 ASXL1 失活和 H3K27me3 减少。
IF 9.3 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-14 DOI: 10.1007/s00401-024-02785-z
Kevin Y. Zhang, Megan Parker, Carly Weber-Levine, Anita Kalluri, Ignacio Gonzalez-Gomez, Eric Raabe, Jonathan C. Dudley, Christopher Gocke, Ming-Tseh Lin, Ying Zou, Mohamed Sherief, David O. Kamson, Matthias Holdhoff, Debraj Mukherjee, Victoria Croog, Karisa C. Schreck, Jordina Rincon-Torroella, Chetan Bettegowda, Charles G. Eberhart, Tejus Bale, Calixto-Hope G. Lucas
{"title":"ASXL1 inactivation and reduced H3K27me3 across central nervous system tumors","authors":"Kevin Y. Zhang,&nbsp;Megan Parker,&nbsp;Carly Weber-Levine,&nbsp;Anita Kalluri,&nbsp;Ignacio Gonzalez-Gomez,&nbsp;Eric Raabe,&nbsp;Jonathan C. Dudley,&nbsp;Christopher Gocke,&nbsp;Ming-Tseh Lin,&nbsp;Ying Zou,&nbsp;Mohamed Sherief,&nbsp;David O. Kamson,&nbsp;Matthias Holdhoff,&nbsp;Debraj Mukherjee,&nbsp;Victoria Croog,&nbsp;Karisa C. Schreck,&nbsp;Jordina Rincon-Torroella,&nbsp;Chetan Bettegowda,&nbsp;Charles G. Eberhart,&nbsp;Tejus Bale,&nbsp;Calixto-Hope G. Lucas","doi":"10.1007/s00401-024-02785-z","DOIUrl":"10.1007/s00401-024-02785-z","url":null,"abstract":"","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":null,"pages":null},"PeriodicalIF":9.3,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11324662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141974780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Loss over 5% of chromosome 1p is a clinically relevant and applicable cut-off for increased risk of recurrence in meningioma 1p 染色体缺失率超过 5%是脑膜瘤复发风险增加的一个临床相关且适用的临界值。
IF 9.3 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-08 DOI: 10.1007/s00401-024-02777-z
Sybren L. N. Maas, Thomas Hielscher, Philipp Sievers, Volker Hovestadt, Abigail K. Suwala, Till Acker, Michael Weller, Matthias Preusser, Christel Herold-Mende, Wolfgang Wick, Andreas von Deimling, Natalie Berghaus, Felix Sahm
{"title":"Loss over 5% of chromosome 1p is a clinically relevant and applicable cut-off for increased risk of recurrence in meningioma","authors":"Sybren L. N. Maas,&nbsp;Thomas Hielscher,&nbsp;Philipp Sievers,&nbsp;Volker Hovestadt,&nbsp;Abigail K. Suwala,&nbsp;Till Acker,&nbsp;Michael Weller,&nbsp;Matthias Preusser,&nbsp;Christel Herold-Mende,&nbsp;Wolfgang Wick,&nbsp;Andreas von Deimling,&nbsp;Natalie Berghaus,&nbsp;Felix Sahm","doi":"10.1007/s00401-024-02777-z","DOIUrl":"10.1007/s00401-024-02777-z","url":null,"abstract":"","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":null,"pages":null},"PeriodicalIF":9.3,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11310275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Analysis of microisolated frontal cortex excitatory layer III and V pyramidal neurons reveals a neurodegenerative phenotype in individuals with Down syndrome 对额叶皮层兴奋层 III 和 V 锥体神经元的微分离分析显示了唐氏综合征患者的神经退行性表型。
IF 9.3 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-06 DOI: 10.1007/s00401-024-02768-0
Melissa J. Alldred, Harshitha Pidikiti, Kyrillos W. Ibrahim, Sang Han Lee, Adriana Heguy, Gabriel E. Hoffman, Panos Roussos, Thomas Wisniewski, Jerzy Wegiel, Grace E. Stutzmann, Elliott J. Mufson, Stephen D. Ginsberg

We elucidated the molecular fingerprint of vulnerable excitatory neurons within select cortical lamina of individuals with Down syndrome (DS) for mechanistic understanding and therapeutic potential that also informs Alzheimer’s disease (AD) pathophysiology. Frontal cortex (BA9) layer III (L3) and layer V (L5) pyramidal neurons were microisolated from postmortem human DS and age- and sex-matched controls (CTR) to interrogate differentially expressed genes (DEGs) and key biological pathways relevant to neurodegenerative programs. We identified > 2300 DEGs exhibiting convergent dysregulation of gene expression in both L3 and L5 pyramidal neurons in individuals with DS versus CTR subjects. DEGs included over 100 triplicated human chromosome 21 genes in L3 and L5 neurons, demonstrating a trisomic neuronal karyotype in both laminae. In addition, thousands of other DEGs were identified, indicating gene dysregulation is not limited to trisomic genes in the aged DS brain, which we postulate is relevant to AD pathobiology. Convergent L3 and L5 DEGs highlighted pertinent biological pathways and identified key pathway-associated targets likely underlying corticocortical neurodegeneration and related cognitive decline in individuals with DS. Select key DEGs were interrogated as potential hub genes driving dysregulation, namely the triplicated DEGs amyloid precursor protein (APP) and superoxide dismutase 1 (SOD1), along with key signaling DEGs including mitogen activated protein kinase 1 and 3 (MAPK1, MAPK3) and calcium calmodulin dependent protein kinase II alpha (CAMK2A), among others. Hub DEGs determined from multiple pathway analyses identified potential therapeutic candidates for amelioration of cortical neuron dysfunction and cognitive decline in DS with translational relevance to AD.

我们阐明了唐氏综合征(DS)患者特定皮层内脆弱兴奋神经元的分子指纹,以便从机理上了解阿尔茨海默病(AD)的病理生理学,并挖掘其治疗潜力。从死后人类唐氏综合征患者和年龄与性别匹配的对照组(CTR)中微分离出额叶皮层(BA9)第III层(L3)和第V层(L5)锥体神经元,以研究与神经退行性疾病相关的差异表达基因(DEGs)和关键生物通路。我们在 DS 患者与 CTR 受试者的 L3 和 L5 锥体神经元中发现了超过 2300 个 DEGs,这些 DEGs 表现出基因表达的趋同失调。在L3和L5神经元中,DEGs包括100多个人类21号染色体三倍体基因,这表明在两个神经元层中都存在三体神经元核型。此外,还发现了数千个其他DEGs,这表明基因失调并不局限于老年DS大脑中的三体基因,我们推测这与AD病理生物学有关。L3和L5 DEGs的融合突显了相关的生物通路,并确定了可能是DS患者皮质神经变性和相关认知能力下降的关键通路相关靶点。研究人员选择了一些关键的 DEGs 作为驱动失调的潜在枢纽基因,即三重 DEGs 淀粉样前体蛋白(APP)和超氧化物歧化酶 1(SOD1),以及关键的信号转导 DEGs,包括丝裂原活化蛋白激酶 1 和 3(MAPK1、MAPK3)以及钙调蛋白依赖性蛋白激酶 II alpha(CAMK2A)等。通过多通路分析确定的枢纽 DEGs 确定了改善 DS 皮质神经元功能障碍和认知能力下降的潜在候选疗法,这些候选疗法与 AD 具有转化相关性。
{"title":"Analysis of microisolated frontal cortex excitatory layer III and V pyramidal neurons reveals a neurodegenerative phenotype in individuals with Down syndrome","authors":"Melissa J. Alldred,&nbsp;Harshitha Pidikiti,&nbsp;Kyrillos W. Ibrahim,&nbsp;Sang Han Lee,&nbsp;Adriana Heguy,&nbsp;Gabriel E. Hoffman,&nbsp;Panos Roussos,&nbsp;Thomas Wisniewski,&nbsp;Jerzy Wegiel,&nbsp;Grace E. Stutzmann,&nbsp;Elliott J. Mufson,&nbsp;Stephen D. Ginsberg","doi":"10.1007/s00401-024-02768-0","DOIUrl":"10.1007/s00401-024-02768-0","url":null,"abstract":"<div><p>We elucidated the molecular fingerprint of vulnerable excitatory neurons within select cortical lamina of individuals with Down syndrome (DS) for mechanistic understanding and therapeutic potential that also informs Alzheimer’s disease (AD) pathophysiology. Frontal cortex (BA9) layer III (L3) and layer V (L5) pyramidal neurons were microisolated from postmortem human DS and age- and sex-matched controls (CTR) to interrogate differentially expressed genes (DEGs) and key biological pathways relevant to neurodegenerative programs. We identified &gt; 2300 DEGs exhibiting convergent dysregulation of gene expression in both L3 and L5 pyramidal neurons in individuals with DS versus CTR subjects. DEGs included over 100 triplicated human chromosome 21 genes in L3 and L5 neurons, demonstrating a trisomic neuronal karyotype in both laminae. In addition, thousands of other DEGs were identified, indicating gene dysregulation is not limited to trisomic genes in the aged DS brain, which we postulate is relevant to AD pathobiology. Convergent L3 and L5 DEGs highlighted pertinent biological pathways and identified key pathway-associated targets likely underlying corticocortical neurodegeneration and related cognitive decline in individuals with DS. Select key DEGs were interrogated as potential hub genes driving dysregulation, namely the triplicated DEGs amyloid precursor protein (APP) and superoxide dismutase 1 (SOD1), along with key signaling DEGs including mitogen activated protein kinase 1 and 3 (MAPK1, MAPK3) and calcium calmodulin dependent protein kinase II alpha (CAMK2A), among others. Hub DEGs determined from multiple pathway analyses identified potential therapeutic candidates for amelioration of cortical neuron dysfunction and cognitive decline in DS with translational relevance to AD.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":null,"pages":null},"PeriodicalIF":9.3,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-024-02768-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer’s disease 淀粉样斑块微环境中小胶质细胞动态增强和 tau 种子减少有助于阿尔茨海默氏症患者的认知恢复能力。
IF 9.3 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-05 DOI: 10.1007/s00401-024-02775-1
Nur Jury-Garfe, Javier Redding-Ochoa, Yanwen You, Pablo Martínez, Hande Karahan, Enrique Chimal-Juárez, Travis S. Johnson, Jie Zhang, Susan Resnick, Jungsu Kim, Juan C. Troncoso, Cristian A. Lasagna-Reeves

Asymptomatic Alzheimer’s disease (AsymAD) describes the status of individuals with preserved cognition but identifiable Alzheimer’s disease (AD) brain pathology (i.e., beta-amyloid (Aβ) deposits, neuritic plaques, and neurofibrillary tangles) at autopsy. In this study, we investigated the postmortem brains of a cohort of AsymAD subjects to gain insight into the mechanisms underlying resilience to AD pathology and cognitive decline. Our results showed that AsymAD cases exhibit enrichment in core plaques, decreased filamentous plaque accumulation, and increased plaque-surrounding microglia. Less pathological tau aggregation in dystrophic neurites was found in AsymAD brains than in AD brains, and tau seeding activity was comparable to that in healthy brains. We used spatial transcriptomics to characterize the plaque niche further and revealed autophagy, endocytosis, and phagocytosis as the pathways associated with the genes upregulated in the AsymAD plaque niche. Furthermore, the levels of ARP2 and CAP1, which are actin-based motility proteins that participate in the dynamics of actin filaments to allow cell motility, were increased in the microglia surrounding amyloid plaques in AsymAD cases. Our findings suggest that the amyloid-plaque microenvironment in AsymAD cases is characterized by the presence of microglia with highly efficient actin-based cell motility mechanisms and decreased tau seeding compared with that in AD brains. These two mechanisms can potentially protect against the toxic cascade initiated by Aβ, preserving brain health, and slowing AD pathology progression.

无症状阿尔茨海默病(AsymAD)是指在尸检时认知能力得到保留,但大脑出现可识别的阿尔茨海默病(AD)病理变化(即β-淀粉样蛋白(Aβ)沉积、神经氨酸斑块和神经纤维缠结)的个体。在这项研究中,我们对一组AsymAD受试者的死后大脑进行了调查,以深入了解AD病理学和认知能力下降的恢复机制。我们的研究结果表明,AsymAD病例的核心斑块富集,丝状斑块堆积减少,斑块周围的小胶质细胞增多。与AD患者相比,AsymAD患者大脑中营养不良神经元的病理tau聚集较少,tau播种活性与健康大脑相当。我们利用空间转录组学进一步描述了斑块龛的特征,发现自噬、内吞和吞噬是与AsymAD斑块龛中基因上调相关的途径。此外,在AsymAD病例中,淀粉样蛋白斑块周围的小胶质细胞中ARP2和CAP1的水平升高,ARP2和CAP1是基于肌动蛋白的运动蛋白,参与肌动蛋白丝的动态变化以实现细胞运动。我们的研究结果表明,与AD病例相比,AsymAD病例中淀粉样蛋白斑块微环境的特点是存在具有高效肌动蛋白细胞运动机制的小胶质细胞,并且tau种子减少。这两种机制有可能抵御由Aβ引发的毒性级联,保护大脑健康,减缓AD病理进展。
{"title":"Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer’s disease","authors":"Nur Jury-Garfe,&nbsp;Javier Redding-Ochoa,&nbsp;Yanwen You,&nbsp;Pablo Martínez,&nbsp;Hande Karahan,&nbsp;Enrique Chimal-Juárez,&nbsp;Travis S. Johnson,&nbsp;Jie Zhang,&nbsp;Susan Resnick,&nbsp;Jungsu Kim,&nbsp;Juan C. Troncoso,&nbsp;Cristian A. Lasagna-Reeves","doi":"10.1007/s00401-024-02775-1","DOIUrl":"10.1007/s00401-024-02775-1","url":null,"abstract":"<div><p>Asymptomatic Alzheimer’s disease (AsymAD) describes the status of individuals with preserved cognition but identifiable Alzheimer’s disease (AD) brain pathology (i.e., beta-amyloid (Aβ) deposits, neuritic plaques, and neurofibrillary tangles) at autopsy. In this study, we investigated the postmortem brains of a cohort of AsymAD subjects to gain insight into the mechanisms underlying resilience to AD pathology and cognitive decline. Our results showed that AsymAD cases exhibit enrichment in core plaques, decreased filamentous plaque accumulation, and increased plaque-surrounding microglia. Less pathological tau aggregation in dystrophic neurites was found in AsymAD brains than in AD brains, and tau seeding activity was comparable to that in healthy brains. We used spatial transcriptomics to characterize the plaque niche further and revealed autophagy, endocytosis, and phagocytosis as the pathways associated with the genes upregulated in the AsymAD plaque niche. Furthermore, the levels of ARP2 and CAP1, which are actin-based motility proteins that participate in the dynamics of actin filaments to allow cell motility, were increased in the microglia surrounding amyloid plaques in AsymAD cases. Our findings suggest that the amyloid-plaque microenvironment in AsymAD cases is characterized by the presence of microglia with highly efficient actin-based cell motility mechanisms and decreased tau seeding compared with that in AD brains. These two mechanisms can potentially protect against the toxic cascade initiated by Aβ, preserving brain health, and slowing AD pathology progression.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":null,"pages":null},"PeriodicalIF":9.3,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Alcohol consumers with liver pathology rarely display α-synuclein pathology 患有肝脏病变的饮酒者很少出现α-突触核蛋白病变。
IF 9.3 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-01 DOI: 10.1007/s00401-024-02772-4
Sylwia Libard, Fredrik Tamsen, Irina Alafuzoff

It has been suggested that alcohol consumption protects against Parkinson's disease (PD). Here we assessed postmortem tissue samples from the brains and livers of 100 subjects with ages at death ranging from 51 to 93. Twenty percent of these subjects were demented. We used standardized assessment strategies to assess both the brain and liver pathologies (LP). Our cohort included subjects with none, mild, moderate, and severe LP caused by alcohol consumption. We noted a significant negative correlation of categorical data between liver steatosis and α-synuclein (αS) in the brain and a significant negative correlation between the extent of liver steatosis and fibrosis and the extent of αS in the brain. There was a significant negative association between the observation of Alzheimer’s type II astrocytes and αS pathology in the brain. No association was noted between LP and hyperphosphorylated τ (HPτ). No significant correlation could be seen between the extent of LP and the extent of HPτ, amyloid β protein (Aβ) or transactive DNA binding protein 43 (TDP43) in the brain. There were significant correlations observed between the extent of HPτ, Aβ, αS, and TDP43 in the brain and between liver steatosis, inflammation, and fibrosis. Subjects with severe LP displayed a higher frequency of Alzheimer’s type II astrocytes compared to those with no, or mild, LP. The assessed protein alterations were not more prevalent or severe in subjects with Alzheimer’s type II astrocytes in the brain. In all cases, dementia was attributed to a combination of altered proteins, i.e., mixed dementia and dementia was observed in 30% of those with mild LP when compared with 13% of those with severe LP. In summary, our results are in line with the outcome obtained by the two recent meta-analyses suggesting that subjects with a history of alcohol consumption seldom develop an α-synucleinopathy.

有人认为,饮酒可预防帕金森病(PD)。在这里,我们对 100 名死亡年龄在 51 岁至 93 岁之间的受试者的大脑和肝脏死后组织样本进行了评估。其中 20% 的受试者患有痴呆症。我们采用标准化的评估策略来评估大脑和肝脏病变(LP)。我们的研究对象包括因饮酒导致的无肝病、轻度肝病、中度肝病和重度肝病。我们注意到,肝脏脂肪变性与大脑中的α-突触核蛋白(αS)之间的分类数据呈显著负相关,肝脏脂肪变性和纤维化程度与大脑中的αS程度呈显著负相关。观察到的阿尔茨海默氏症 II 型星形胶质细胞与大脑中的αS 病理之间存在明显的负相关。LP与高磷酸化τ(HPτ)之间没有关联。LP的程度与大脑中HPτ、淀粉样β蛋白(Aβ)或转录DNA结合蛋白43(TDP43)的程度之间没有明显的相关性。观察发现,大脑中HPτ、Aβ、αS和TDP43的程度与肝脏脂肪变性、炎症和纤维化之间存在明显的相关性。与无肝硬化或轻度肝硬化的受试者相比,重度肝硬化受试者出现阿尔茨海默氏症II型星形胶质细胞的频率更高。在脑内有阿尔茨海默氏症 II 型星形胶质细胞的受试者中,所评估的蛋白质变化并不更普遍或更严重。在所有病例中,痴呆都是由于蛋白质的综合改变造成的,即混合痴呆,在轻度 LP 患者中,有 30% 的人出现痴呆,而在重度 LP 患者中,只有 13% 的人出现痴呆。总之,我们的研究结果与最近两项荟萃分析得出的结果一致,即有饮酒史的受试者很少发生α-突触核蛋白病。
{"title":"Alcohol consumers with liver pathology rarely display α-synuclein pathology","authors":"Sylwia Libard,&nbsp;Fredrik Tamsen,&nbsp;Irina Alafuzoff","doi":"10.1007/s00401-024-02772-4","DOIUrl":"10.1007/s00401-024-02772-4","url":null,"abstract":"<div><p>It has been suggested that alcohol consumption protects against Parkinson's disease (PD). Here we assessed postmortem tissue samples from the brains and livers of 100 subjects with ages at death ranging from 51 to 93. Twenty percent of these subjects were demented. We used standardized assessment strategies to assess both the brain and liver pathologies (LP). Our cohort included subjects with none, mild, moderate, and severe LP caused by alcohol consumption. We noted a significant negative correlation of categorical data between liver steatosis and α-synuclein (αS) in the brain and a significant negative correlation between the extent of liver steatosis and fibrosis and the extent of αS in the brain. There was a significant negative association between the observation of Alzheimer’s type II astrocytes and αS pathology in the brain. No association was noted between LP and hyperphosphorylated τ (HPτ). No significant correlation could be seen between the extent of LP and the extent of HPτ, amyloid β protein (Aβ) or transactive DNA binding protein 43 (TDP43) in the brain. There were significant correlations observed between the extent of HPτ, Aβ, αS, and TDP43 in the brain and between liver steatosis, inflammation, and fibrosis. Subjects with severe LP displayed a higher frequency of Alzheimer’s type II astrocytes compared to those with no, or mild, LP. The assessed protein alterations were not more prevalent or severe in subjects with Alzheimer’s type II astrocytes in the brain. In all cases, dementia was attributed to a combination of altered proteins, i.e., mixed dementia and dementia was observed in 30% of those with mild LP when compared with 13% of those with severe LP. In summary, our results are in line with the outcome obtained by the two recent meta-analyses suggesting that subjects with a history of alcohol consumption seldom develop an α-synucleinopathy.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":null,"pages":null},"PeriodicalIF":9.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11291549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The parkin V380L variant is a genetic modifier of Machado–Joseph disease with impact on mitophagy Parkin V380L 变体是马查多-约瑟夫病的遗传修饰因子,对有丝分裂有影响。
IF 9.3 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-01 DOI: 10.1007/s00401-024-02762-6
Jonasz J. Weber, Leah Czisch, Priscila Pereira Sena, Florian Fath, Chrisovalantou Huridou, Natasa Schwarz, Rana D. Incebacak Eltemur, Anna Würth, Daniel Weishäupl, Miriam Döcker, Gunnar Blumenstock, Sandra Martins, Jorge Sequeiros, Guy A. Rouleau, Laura Bannach Jardim, Maria-Luiza Saraiva-Pereira, Marcondes C. França Jr., Carlos R. Gordon, Roy Zaltzman, Mario R. Cornejo-Olivas, Bart P. C. van de Warrenburg, Alexandra Durr, Alexis Brice, Peter Bauer, Thomas Klockgether, Ludger Schöls, Olaf Riess, The EUROSCA Network, Thorsten Schmidt

Machado–Joseph disease (MJD) is an autosomal dominant neurodegenerative spinocerebellar ataxia caused by a polyglutamine-coding CAG repeat expansion in the ATXN3 gene. While the CAG length correlates negatively with the age at onset, it accounts for approximately 50% of its variability only. Despite larger efforts in identifying contributing genetic factors, candidate genes with a robust and plausible impact on the molecular pathogenesis of MJD are scarce. Therefore, we analysed missense single nucleotide polymorphism variants in the PRKN gene encoding the Parkinson's disease-associated E3 ubiquitin ligase parkin, which is a well-described interaction partner of the MJD protein ataxin-3, a deubiquitinase. By performing a correlation analysis in the to-date largest MJD cohort of more than 900 individuals, we identified the V380L variant as a relevant factor, decreasing the age at onset by 3 years in homozygous carriers. Functional analysis in an MJD cell model demonstrated that parkin V380L did not modulate soluble or aggregate levels of ataxin-3 but reduced the interaction of the two proteins. Moreover, the presence of parkin V380L interfered with the execution of mitophagy—the autophagic removal of surplus or damaged mitochondria—thereby compromising cell viability. In summary, we identified the V380L variant in parkin as a genetic modifier of MJD, with negative repercussions on its molecular pathogenesis and disease age at onset.

马查多-约瑟夫病(MJD)是一种常染色体显性神经退行性脊髓小脑共济失调症,由 ATXN3 基因中多聚谷氨酰胺编码的 CAG 重复扩增引起。虽然CAG长度与发病年龄呈负相关,但只占其变异性的约50%。尽管在确定遗传因素方面做了大量工作,但对 MJD 分子发病机制具有可靠和可信影响的候选基因仍然很少。因此,我们分析了编码帕金森病相关 E3 泛素连接酶 parkin 的 PRKN 基因中的错义单核苷酸多态性变异。通过对迄今为止最大的由 900 多人组成的 MJD 群体进行相关性分析,我们发现 V380L 变异是一个相关因素,它使同卵携带者的发病年龄降低了 3 岁。在一个 MJD 细胞模型中进行的功能分析表明,parkin V380L 不会调节共济失调蛋白-3 的可溶性或聚集水平,但会降低这两种蛋白的相互作用。此外,parkin V380L 的存在干扰了有丝分裂--自噬清除多余或受损线粒体--的执行,从而损害了细胞的活力。总之,我们发现 Parkin V380L 变体是 MJD 的遗传修饰因子,对其分子发病机制和发病年龄有负面影响。
{"title":"The parkin V380L variant is a genetic modifier of Machado–Joseph disease with impact on mitophagy","authors":"Jonasz J. Weber,&nbsp;Leah Czisch,&nbsp;Priscila Pereira Sena,&nbsp;Florian Fath,&nbsp;Chrisovalantou Huridou,&nbsp;Natasa Schwarz,&nbsp;Rana D. Incebacak Eltemur,&nbsp;Anna Würth,&nbsp;Daniel Weishäupl,&nbsp;Miriam Döcker,&nbsp;Gunnar Blumenstock,&nbsp;Sandra Martins,&nbsp;Jorge Sequeiros,&nbsp;Guy A. Rouleau,&nbsp;Laura Bannach Jardim,&nbsp;Maria-Luiza Saraiva-Pereira,&nbsp;Marcondes C. França Jr.,&nbsp;Carlos R. Gordon,&nbsp;Roy Zaltzman,&nbsp;Mario R. Cornejo-Olivas,&nbsp;Bart P. C. van de Warrenburg,&nbsp;Alexandra Durr,&nbsp;Alexis Brice,&nbsp;Peter Bauer,&nbsp;Thomas Klockgether,&nbsp;Ludger Schöls,&nbsp;Olaf Riess,&nbsp;The EUROSCA Network,&nbsp;Thorsten Schmidt","doi":"10.1007/s00401-024-02762-6","DOIUrl":"10.1007/s00401-024-02762-6","url":null,"abstract":"<div><p>Machado–Joseph disease (MJD) is an autosomal dominant neurodegenerative spinocerebellar ataxia caused by a polyglutamine-coding CAG repeat expansion in the <i>ATXN3</i> gene. While the CAG length correlates negatively with the age at onset, it accounts for approximately 50% of its variability only. Despite larger efforts in identifying contributing genetic factors, candidate genes with a robust and plausible impact on the molecular pathogenesis of MJD are scarce. Therefore, we analysed missense single nucleotide polymorphism variants in the <i>PRKN</i> gene encoding the Parkinson's disease-associated E3 ubiquitin ligase parkin, which is a well-described interaction partner of the MJD protein ataxin-3, a deubiquitinase. By performing a correlation analysis in the to-date largest MJD cohort of more than 900 individuals, we identified the V380L variant as a relevant factor, decreasing the age at onset by 3 years in homozygous carriers. Functional analysis in an MJD cell model demonstrated that parkin V380L did not modulate soluble or aggregate levels of ataxin-3 but reduced the interaction of the two proteins. Moreover, the presence of parkin V380L interfered with the execution of mitophagy—the autophagic removal of surplus or damaged mitochondria—thereby compromising cell viability. In summary, we identified the V380L variant in parkin as a genetic modifier of MJD, with negative repercussions on its molecular pathogenesis and disease age at onset.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":null,"pages":null},"PeriodicalIF":9.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11294389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Diffuse, IDH-wildtype gliomas in adults with minimal histological change and isolated TERT promoter mutation: not simply CNS WHO grade 4 组织学变化极小的弥漫性 IDH 野生型成人胶质瘤和孤立的 TERT 启动子突变:不仅仅是中枢神经系统 WHO 4 级。
IF 9.3 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-07-29 DOI: 10.1007/s00401-024-02773-3
L. P. Priesterbach-Ackley, F. Cordier, P. de Witt Hamer, T. J. Snijders, P. A. Robe, B. Küsters, W. W. J. de Leng, W. F. A. den Dunnen, D. Brandsma, C. Jansen, P. Wesseling, A. Muhlebner
{"title":"Diffuse, IDH-wildtype gliomas in adults with minimal histological change and isolated TERT promoter mutation: not simply CNS WHO grade 4","authors":"L. P. Priesterbach-Ackley,&nbsp;F. Cordier,&nbsp;P. de Witt Hamer,&nbsp;T. J. Snijders,&nbsp;P. A. Robe,&nbsp;B. Küsters,&nbsp;W. W. J. de Leng,&nbsp;W. F. A. den Dunnen,&nbsp;D. Brandsma,&nbsp;C. Jansen,&nbsp;P. Wesseling,&nbsp;A. Muhlebner","doi":"10.1007/s00401-024-02773-3","DOIUrl":"10.1007/s00401-024-02773-3","url":null,"abstract":"","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":null,"pages":null},"PeriodicalIF":9.3,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Acta Neuropathologica
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1